Fecal Transplants: They Work, the Regulations Don’t

Lara Thompson was 26 when her life fell apart.

She was living in Rhode Island and working in HIV prevention research when she unexpectedly developed nausea and diarrhea. It was early 2008, a few weeks after New Year’s, and she thought she might have picked up a stomach virus at a holiday gathering, or stressed her system with overindulgence. She expected the symptoms would pass after a few days. They didn’t.

“In three weeks, I dropped 15-20 pounds,” she says now. “I couldn’t keep anything in; I would have to run to the bathroom at a moment’s notice. I was so lethargic I had to stay home from work.”

When she consulted her doctor, she found out what was bothering her was more complex than a virus. Somehow, her intestinal lining had become infected with Clostridium difficile, or C. diff, a tough and persistent bacterium that has been rising in incidence and gaining antibiotic resistance, becoming increasingly difficult to treat.

Her infection conformed to that trend. First she took Flagyl, which left her nauseated and gave her migraines. When the diarrhea never abated, her physicians switched her to high doses of vancomycin, a last-resort, broad-spectrum big gun that so disrupted her system that she developed yeast infections throughout her body. The C. diff persisted, and her workplace asked her to take a leave of absence, worried not only for her health but for the possibility she might pass the infection to the HIV-positive patients she worked with.

For months, physicians kept trying different drug regimens, while Thompson’s hair fell out and her muscles wasted. By summer, she was down 40 pounds and close to desperate. Scouring the internet for alternatives, she found a description of a treatment that didn’t use drugs. It was a fecal transplant, which is just what it sounds like: inserting strained, diluted feces harvested from someone with a healthy gut into the sick person’s large intestine, in hopes of replacing the devastated colony of bacteria living there with a fresh, robust one.

“It made sense to me,” Thompson says now. “And I had no other options. I was getting sicker, basically living in the bathroom, crying, emotional all the time.”

She gathered everything she could print out, and found a doctor who was friendly to the procedure: Colleen Kelly, a gastroenterologist based in Providence. In late October 2008, Kelly performed the transplant as an outpatient procedure, after Thompson had done the clean-out preparations that someone does to get ready for a colonoscopy. Her boyfriend was her donor.

In two hours, she started feeling better. In three years, her C. diff has never recurred.

Thompson is one of a number of fecal-transplant recipients I talked to for a piece I have this month in Scientific American, my first installment in a column I’ll be writing for them called “The Science of Health.” (I’m sharing the column with Deborah Franklin, another longtime health journalist; we are edited by Christine Gorman and Ferris Jabr.) In that piece — please take a look — I talk to a number of patients and physicians, including Kelly, who is leading the charge to get the transplants researched and standardized.

… Fecal transplants remain a niche therapy, practiced only by gastroenterologists who work for broad-minded institutions and who have overcome the ick factor. To become widely accepted, recommended by professional societies and reimbursed by insurers, the transplants will need to be rigorously studied in a randomized clinical trial, in which people taking a treatment are assessed alongside people who are not.

Kelly and several others have drafted a trial design to submit to the National Institutes of Health for grant funding. Yet an unexpected obstacle stands in their way: before the NIH approves any trial, the substance being studied must be granted “investigational” status by the Food and Drug Administration. The main categories under which the FDA considers things to be investigated are drugs, devices, and biological products such as vaccines and tissues. Feces simply do not fit into any of those categories.

So, to be clear, what we have is a treatment that is minimally invasive, reliable, cheap, and with a long clinical history: The earliest documented use in humans goes back to 1958, and it has a longer and still current use in veterinary medicine, especially in racehorses. Also, it works, in more than 9 out of 10 patients. Kelly told me: “There is no drug, for anything” with a cure rate routinely that high.

And yet, because of this regulatory conundrum, the only physicians practicing it are ones whose institutions are tolerant of their performing an unofficially experimental procedure, and who are strong-stomached enough to get past our evolutionarily hard-wired distaste for dung. So far, only about a dozen U.S. physicians have admitted — via publishing their case series in medical journals — to performing fecal transplants, though the procedure’s much more widely accepted in Australia and Europe.

Support is growing, though. In the several months since I filed the column (magazines, unlike blogs, have a multi-month production process), here’s what has happened:

At the American College of Gastroenterology’s annual meeting in October, a group of researchers that included Dr. Lawrence Brandt of Montefiore Medical Center in the Bronx, one of the US pioneers of the procedure, reported that 70 out of 77 patients in five states who had had the procedure at least 3 months earlier (mean was 17 months) had no recurrences, a cure rate of 91 percent. (NB: The abstracts are apparently not linkable, but you can search for them on this page.)

At the same meeting, researchers from Ohio, Michigan and Norway reported on a meta-analysis of 16 case-reports and case-series, which found a cure rate of 85 percent in 148 patients. (Mean time since the procedure was 12 months.)

In the Nov. 15 issue of Clinical Infectious Diseases, another meta-analysis — this time of 317 patients in 27 case series — found a cure rate of 92 percent.

And in the December issue of Clinical Gastroenterology and Hepatology, a group of researchers who call themselves the Fecal Microbiota Transplantation Workgroup, and who represent the leading practitioners of the procedure in the US and Australia (including Kelly and Brandt), present guidelines for other physicians who want to begin using it. Clinical Gastroenterology and Hepatology is the clinical-practice journal of the American Gastroenterological Association, so publication there represents a degree of professional recognition and acceptance regardless of regulatory action.

It is worth mentioning that, in every case covered by those papers, patients were treated for recurrent C. diff that had already resisted multiple rounds of antibiotic treatment — which, as my SciAm piece explains, is remarkably common. Yet some practitioners, including Brandt, argue that it should be not a last-gasp treatment, but because it is so inexpensive and safe, the first thing doctors ought to try. And other researchers, notably Borody of Australia, have gone beyond C. diff and are trialing fecal transplants for other conditions such as Crohn’s disease.

Moreover, since a fecal transplant is essentially a replacement of the gut microbiome with a healthier community of gut flora, other research is considering whether it can be applied to the other conditions that the microbiome is now believed to influence, including obesity and depression.

But what about the regulatory, ahem, logjam? Just last week, Kelly, Thompson’s doctor, sent to the FDA a first draft of an application to grant fecal transplants the investigational status necessary for research to proceed. That process will bear watching.

I wonder, though. You can’t monetize feces: They are abundant, free and and essentially unpatentable, making it unlikely that pharmaceutical companies, the major funders of US biomedical research, would support research involving them. But, admittedly, feces are unavoidably disgusting. So what if there were a feces transplant that was not disgusting, because it did not, in fact, use feces? A pharma company can’t patent stool — but it could certainly patent, and charge a high price for, a universal stool replacement that contained some optimal combination of the major types of gut flora needed to restore intestinal health.

I hasten to add: That’s just my hypothetical. I don’t know of any research into artificial stool intended for use in recurrent C. diff. But if I had to put money on whether some smart pharma company somewhere hasn’t already spotted that opportunity, I wouldn’t take that bet.